Affiliation:
1. Departamento de Genética, Facultad de Biologia, Universidad de Sevilla, Sevilla, Spain
Abstract
ABSTRACT
THO/TREX is a conserved, eukaryotic protein complex operating at the interface between transcription and messenger ribonucleoprotein (mRNP) metabolism. THO mutations impair transcription and lead to increased transcription-associated recombination (TAR). These phenotypes are dependent on the nascent mRNA; however, the molecular mechanism by which impaired mRNP biogenesis triggers recombination in THO/TREX mutants is unknown. In this study, we provide evidence that deficient mRNP biogenesis causes slowdown or pausing of the replication fork in
hpr1Δ
mutants. Impaired replication appears to depend on sequence-specific features since it was observed upon activation of
lacZ
but not
leu2
transcription. Replication fork progression could be partially restored by hammerhead ribozyme-guided self-cleavage of the nascent mRNA. Additionally,
hpr1Δ
increased the number of S-phase but not G
2
-dependent TAR events as well as the number of budded cells containing Rad52 repair foci. Our results link transcription-dependent genomic instability in THO mutants with impaired replication fork progression, suggesting a molecular basis for a connection between inefficient mRNP biogenesis and genetic instability.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
139 articles.
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